Visual estimation of pulse pressure variation is not reliable: a randomized simulation study.

Pulse pressure variation (PPV) can be monitored several ways, but according to recent survey data it is most often visually estimated ("eyeballed") by practitioners. It is not known how accurate visual estimation of PPV is, or whether eyeballing of PPV in goal-directed fluid therapy studies may limit the ability to blind the control group to PPV value. The goal of this study was to test the accuracy of visual estimation of PPV. Using a simulator program designed by the authors that runs on a PC, 20 residents and 19 attendings were shown five arterial pressure waveforms each with different PPV values (range 1-30 %) moving at one of three sweep speeds (6.25, 12.5, or 25 mm/s) and asked to determine the PPV. There was a weak but significant relationship between true PPV and eyeball PPV (r (2) = 0.22; p < 0.01). The agreement between true PPV and eyeball PPV was 3.3 ± 8.7 %. The mean percent error was 122 %. The rate of correct response group classification was 65 %. Mean percent error was higher the faster the waveform sweep speed (130 % at 25 mm/s vs. 117 % at 6.25 mm/s), and correct responsiveness classification lower (58 % at 25 mm/s vs. 69 % at 6.25 mm/s). The results from this study show that eyeballing the arterial pressure waveform in order to evaluate pulse pressure variation is not accurate.

Osteopontin enhances HIV replication and is increased in the brain and cerebrospinal fluid of HIV-infected individuals.

Despite effective and widely available suppressive anti-HIV therapy, the prevalence of mild neurocognitive dysfunction continues to increase. HIV-associated neurocognitive disorder (HAND) is a multifactorial disease with sustained central nervous system inflammation and immune activation as prominent features. Inflammatory macrophages, HIV-infected and uninfected, play a central role in the development of HIV dementia. There is a critical need to identify biomarkers and to better understand the molecular mechanisms leading to cognitive dysfunction in HAND. In this regard, we identified through a subtractive hybridization strategy osteopontin (OPN, SPP1, gene) an inflammatory marker, as an upregulated gene in HIV-infected primary human monocyte-derived macrophages. Knockdown of OPN in primary macrophages resulted in a threefold decrease in HIV-1 replication. Ectopic expression of OPN in the TZM-bl cell line significantly enhanced HIV infectivity and replication. A significant increase in the degradation of the NF-κB inhibitor, IκBα and an increase in the nuclear-to-cytoplasmic ratio of NF-κB were found in HIV-infected cells expressing OPN compared to controls. Moreover, mutation of the NF-κB binding domain in the HIV-LTR abrogated enhanced promoter activity stimulated by OPN. Interestingly, compared to cerebrospinal fluid from normal and multiple sclerosis controls, OPN levels were significantly higher in HIV-infected individuals both with and without neurocognitive disorder. OPN levels were highest in HIV-infected individuals with moderate to severe cognitive impairment. Moreover, OPN was significantly elevated in brain tissue from HIV-infected individuals with cognitive disorder versus those without impairment. Collectively, these data suggest that OPN stimulates HIV-1 replication and that high levels of OPN are present in the CNS compartment of HIV-infected individuals, reflecting ongoing inflammatory processes at this site despite anti-HIV therapy.